A Phase 1, Partially Blinded, Placebo-Controlled, Pharmacokinetic Study of Intravenously Administered BMS-943539-01-001 in Healthy Male Volunteers
A Phase 1, Partially Blinded, Placebo-Controlled, study of Intravenously Administered BMS-943539 to assess the pharmacokinetics and in particular the mean T-HALF of BMS-943539 across all doses in healthy male subjects.
Bristol-Myers Squibb Australia
37 participants
Jan 31, 2011
Interventional
Conditions
Summary
BMS-943539 is a non-therapeutic Adnectin (Trademark) with binding affinity for human serum albumin (HSA). It is intended to serve as an albumin binder to extend the serum half-life (T-HALF) when integrated into a single polypeptide chain with a separate therapeutic Adnectin or other protein that would otherwise be rapidly eliminated. Cohorts of subjects will be treated with 0.1, 0.3, or 1.0 mg/kg BMS-943539 or placebo once every two weeks for a total of two drug administrations.
Eligibility
Inclusion Criteria10
- Signed Written Informed Consent
- a) The signed informed consent form.
- Target Population
- a) Healthy subjects as determined by no clinically significant deviation from normal
- in medical history, physical examination, vital signs, electrocardiograms (ECGs),
- and clinical laboratory determinations.
- b) Not using prescription (including topical skin preparations other than nonprescription
- moisturizers) or over-the-counter medications; herbal supplements;
- or drugs of abuse, including alcohol and tobacco, for the duration of participation
- in the study (screening duration plus 56 days following first administration of
Exclusion Criteria22
- c) Agree not to donate blood or plasma to any blood bank or for any purpose (other
- than this study) for the duration of participation in the study (screening duration
- plus 56 days following first administration of blinded study treatment). (See also
- related exclusion criterion 2g.)
- d) Body Mass Index (BMI) of 18 to 32 kg/m2 (BMI=weight (kg)/[height(m)]2) and
- weight no less than 50 kg.
- Age and Reproductive Status
- a) Men, aged 18 to 60 years.
- b) Subjects who are sexually active must agree to use a barrier method of
- contraception during the study and for no less than 45 days following the last
- dose.
- Target Disease Exceptions
- a) Chronic medical conditions requiring ongoing professional medical attention or treatment.
- Medical History and Concurrent Diseases
- a) Any history of autoimmune disease.
- b) Recent (within 6 months) drug or alcohol abuse as defined by DSM IV, Diagnostic Criteria for Drug and Alcohol Abuse
- c) Use of nicotine or tobacco containing products (including but not limited to: snuff, chewing tobacco, cigars, cigarettes, pipes, or nicotine patches) within 6 months prior to investigational product administration and during the study;
- d) Major surgery within 6 months of treatment Day 1.
- e) Concurrent or use within 12 months of treatment day 1 of corticosteroids or other immunosuppressant drugs, with the exception of inhaled or topical corticosteroids, for which there must be no concurrent use or use within 3 months of treatment day 1.
- f) Use of prescription medication within 7 days or 5 x the elimination T-HALF, whichever is longer, before treatment Day 1.
- g) Donation of blood or plasma to a blood bank or in a clinical study (except a screening visit) within 4 weeks of study drug administration.
- h) Blood transfusion within 4 weeks of study drug administration.
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Interventions
All consented patients would be screened up to 14 days prior to randomization. At screening the patients will be assessed on their suitability to enter the study. Assessments preformed include: medical history, physical exam, laboratory assessment, ECG, concomitant and adverse events. Eligable subjects will be randomized. Patients randomised to receive BMS-943539 will be administered the study drug via IV at day 1 and day 15 at different dose levels according to cohort. Cohort 1 will receive 0.1mg/kg. Cohort 2 will receive 0.3mg/Kg. Cohort 3 will receive 1.0mg/Kg Patients will be observed after the 1st infusion on day 1 (observation period 1) and also after the second infusion day 15 (observation period 2). After all the subjects in Cohort 1 have completed their Day 29 visits; the PK findings have been assessed (expected up to 4 weeks); and assuming criteria surpassing the defined no observed adverse event level (NOAEL) have not been met (see below), Cohort 2 will begin the study. Similarly, Cohort 3 will not begin until completion and PK assessment of Cohort 2, assuming the NOAEL has not been surpassed. The NOAEL will be defined as the dose level 1 level below the lowest dose level in which either a) 2 or more actively treated (non-placebo) subjects experience any grade 2 National Cancer Institute (NCI; US)-Common Terminology Criteria for Adverse Events (CTCAE v4.03) BMS-943539-related toxicity or b) at least 1 actively treated subject experiences any grade greater than or equal to 3 BMS-943539-related toxicity. The NOAEL will be the highest dose level completed if neither of these criteria is met. In the case that NOAEL criteria are surpassed in Cohorts 2 or 3, the next lower cohort will be declared the NOAEL and all remaining subjects will be treated at the NOAEL, such that a total of 37 subjects (28 receiving BMS and 9 receiving placebo) are treated in the study. This is in order to maintain the statistical precision sought to support the pharmacokinetic (PK) and immunogenicity research hypotheses, and to support an adequate number of subjects with safety observations. If the dose level of Cohort 1 is found to exceed the NOAEL, then no additional subjects will be dosed and the study will terminate.
Locations(1)
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ACTRN12610001043022